The aim of this proposal is to pursue an examination of the sympathetic modulation of biochemical activity in the rat pineal. Specifically, I seek to pharmacologically characterize the adrenergic receptors that mediate changes in N-acethytransferase activity (NAT) in the rat pineal, particularly those responsible for decreases in enzyme activity, and to characterize some of the changes that occur in these receptors with the development of supersensitivity. To do this, freshly extracted rat pineals will be cultured for about 6 hours in the presence and absence of various adrenergic agents. At the end of this incubation period the pineals will be homogenized and variations in NAT activity will be determined by radioenzymatic assay. Alternatively, in an in vivo model, rats will be pretreated with drugs prior to sacrifice and assay of their pineals for NAT activity. The long term goals of this project is to provide a better understanding of the sympathetic nervous system. Consequently, it is of particular relevance medially to the understanding and treatment of certain types of hypertension and to other diseases which involve the sympathetic nervous system--like the shy-Drager syndrome. Furthermore, it is likely that the mechanisms of sympathetic regulation revealed by this project will be generalizable to the understanding of adrenergic and noradrenergic pathways within the central nervous system and will be of importance in furthering understanding of illnesses like depression, and bipolar illness where central adrenergic mechanisms have been implicated.